SERINE PALMITOYLTRANSFERASE IS THE PRIMARY TARGET OF A SPHINGOSINE-LIKE IMMUNOSUPPRESSANT, ISP-1/MYRIOCIN

被引：473

作者：

MIYAKE, Y ^{[1
]}

KOZUTSUMI, Y ^{[1
]}

NAKAMURA, S ^{[1
]}

FUJITA, T ^{[1
]}

KAWASAKI, T ^{[1
]}

机构：

[1] KYOTO UNIV,FAC PHARMACEUT SCI,DEPT BIOL CHEM,SAKYO KU,KYOTO 606,JAPAN

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1995年 / 211卷 / 02期

关键词：

D O I：

10.1006/bbrc.1995.1827

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

ISP-1/myriocin is a new type of remarkably potent immunosuppressant, the structure of which is homologous to sphingosine, ISP-1/myriocin inhibited the proliferation of an IL-2-dependent mouse cytotoxic T cell line, CTLL-2, at nanomole concentrations. ISP-1/myriocin inhibits serine palmitoyltransferase activity at picomole concentrations. This enzyme catalyzes the first step of sphingolipid biosynthesis and reduces the intracellular pool of sphingolipid intermediates. The growth inhibition induced by ISP-1/myriocin was completely abolished by the addition of sphingosines or sphingosine-1-phosphate, but not by sphingomyelin or glycosphingolipids. These results suggest that sphingosines or sphingosine-1-phosphate are associated with CTLL-2 proliferation, and ISP-1/myriocin suppresses T cell proliferation by the modulation of sphingolipid metabolism, ISP-1/myriocin should be a useful tool for the study of the sphingolipid pathway, which has been associated with various kinds of signal transduction. (C) 1995 Academic Press, Inc.

引用

页码：396 / 403

页数：8

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